Value of podoplanin as an immunohistochemical marker in tumor diagnosis: a review and update

Our plain-English summary of Value of podoplanin as an immunohistochemical marker in tumor diagnosis: a review and update, by N.G. Ordóñez (Applied Immunohistochemistry & Molecular Morphology, 2014).

The study

• Author: N.G. Ordóñez
• Journal: Applied Immunohistochemistry & Molecular Morphology
• Published: 2014;22(5):331-47
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Podoplanin is a type I integral membrane glycoprotein that, because it is expressed in lymphatic endothelium, but not in vascular blood vessel endothelial cells, is commonly used in the identification of lymphatic endothelial differentiation in vascular endothelial neoplasms and lymphatic invasion by tumor. Because podoplanin is also expressed in mesothelial cells and fetal gonocytes, it has proved to be a useful marker for assisting in the differential diagnosis of mesotheliomas and germ cell tumors, particularly seminomas/dysgerminomas. Podoplanin expression has also been reported in a wide variety of other neoplasms, including hemangioblastomas, meningiomas, cartilaginous tumors, and follicular dendritic cell neoplasms. This article reviews the information that is currently available on the application of podoplanin immunostaining in diagnostic pathology.

In plain English

This was a single-author review of published laboratory studies on podoplanin. Podoplanin is a protein that pathologists detect with tissue stains, mostly the D2-40 antibody, to help identify tumors. The review did not study asbestos exposure but covered many tumors, including mesothelioma. Pooling 10 studies, the author reported 449 (79%) of 568 epithelioid mesotheliomas positive. In 8 studies, 19 (6%) of 316 lung adenocarcinomas showed focal staining. The author wrote that podoplanin seemed somewhat less sensitive than calretinin, another mesothelioma marker, but seemed more specific against lung adenocarcinomas. Reported sarcomatoid mesothelioma positivity reached 79% in some studies. The author wrote that this staining is difficult to interpret and, in the author's experience, has no practical value in telling sarcomatoid mesotheliomas from other spindle cell tumors, particularly compared with calretinin. Cited studies indicated that podoplanin did not help separate epithelioid mesothelioma from lung squamous cell carcinoma. The author wrote it had little or no practical utility for separating papillary serous carcinomas from peritoneal epithelioid mesotheliomas. The review also reported staining in 123 (98%) of 125 pure seminomas and 122 of 124 Kaposi sarcomas.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published immunohistochemistry studies, by a single author; no new cases were studied
• Who was studied: Published studies of podoplanin staining in human tumors and normal tissues, including mesotheliomas, adenomatoid tumors, lung and ovarian carcinomas, germ cell tumors, vascular, brain, bone, skin and soft tissue tumors; results pooled in tables
• Exposure: No asbestos exposure was studied. The review concerns podoplanin immunostaining as a diagnostic marker, mostly using the D2-40 monoclonal antibody
• Main results:
  • Epithelioid mesotheliomas: in a combined review of 568 cases from 10 published studies stained with D2-40, 449 (79%) were reported positive
  • Lung adenocarcinomas: in a combined review of 316 cases from 8 published studies, 19 (6%) showed focal reactivity
  • The author wrote that podoplanin seems somewhat less sensitive than calretinin for epithelioid mesothelioma. Its specificity seems higher, because calretinin expression in lung adenocarcinomas has been reported in 3% to 23%
  • Sarcomatoid mesotheliomas: reported positivity ranged from 0% in some studies up to 79% in others. The pooled table shows 70 positive of 228 (31%)
  • In the author's experience, podoplanin staining has no practical value for the differential diagnosis of sarcomatoid mesotheliomas (telling them from other spindle cell tumors), particularly when compared with calretinin
  • In a 2006 study by the same author, 28 (93%) of 30 epithelioid mesotheliomas and 15 (50%) of 30 squamous cell carcinomas of the lung were podoplanin positive
  • Papillary serous carcinomas: 60 (29%) of 206 were positive. The author wrote that these results indicate podoplanin has little or no practical utility in distinguishing them from peritoneal epithelioid mesotheliomas
  • Seminomas: in a combined review of 7 studies, 123 (98%) of 125 pure seminomas and 26 (100%) of 26 mixed germ cell tumors with a seminoma component were positive
  • Kaposi sarcoma: in a combined review of 124 cases from 7 published studies, 122 were reported positive (given as 99% in the text, 98% in Table 1)
• The authors' conclusion: The author concluded that podoplanin is commonly used to identify lymphatic endothelium and has proved useful in the differential diagnosis of mesotheliomas and germ cell tumors, particularly seminomas and dysgerminomas
• Limitations the authors state:
  • The author stated that staining in sarcomatoid mesotheliomas is difficult to interpret. Reasons given were cytoplasmic staining with high background, and staining of reactive cells and lymphatics
  • The author noted that published studies on the lymphatic markers PROX1 and LYVE-1 in vascular tumors are limited, with no comparative studies against podoplanin
  • For several tumor types, such as small cell osteosarcoma versus Ewing sarcoma, the author stated that additional studies are needed to confirm the findings

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Podoplanin (D2-40), Glycoprotein, Neoplasm, Mesothelial Cells, Differential Diagnosis, Mesothelioma, Germ Cell Tumor, Pathology.

Related studies

• Podoplanin is Positive Not Only on Follicular Dendritic Cells and Their Tumoral Counterparts, But Also on Reticular Fibroblasts and in Some Tumors of Reticular Fibroblasts — D. Suárez-Vilela, F.M. Izquierdo (2016)
• Expression of podoplanin and calretinin in meningioma: an immunohistochemical study — M. Shintaku, T. Honda, et al. (2010)
• Podoplanin is a useful marker for identifying mesothelioma in malignant effusions — A. Hanna, Y. Pang, et al. (2010)
• Mediastinal and pleuropulmonary myeloid sarcoma with HBME1 and podoplanin expression. A diagnostic pitfall — D. Suárez-Vilela, F.M. Izquierdo (2020)
• RNA-binding protein LIN28 is a marker for primary extragonadal germ cell tumors: an immunohistochemical study of 131 cases — D. Cao, A. Liu, et al. (2011)
• Vascular endothelial growth factor receptor 2 as a marker for malignant vascular tumors and mesothelioma: an immunohistochemical study of 262 vascular endothelial and 1640 nonvascular tumors — M. Miettinen, M.S. Rikala, et al. (2012)

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